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Study of cytoplasmic and mitochondrial HSP70 chaperones from of Plasmodium falciparum and Leishmania braziliensis and their interaction with co-chaperones and potential ligands/inhibitors

Grant number: 13/16813-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2014
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Julio Cesar Borges
Grantee:Lilian Luzia Beloti
Home Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
Associated research grant:12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis, AP.TEM

Abstract

The molecular chaperones or heat shock proteins (Hsp) are a large family of proteins that assist the correct protein folding. Besides, they avoid the deleterious effect of mutations and accumulations of toxic aggregates in cells under stress. Among the chaperones, Hsp70 is one of the largest and most versatile proteins. The Hsp70 perform several functional processes which include: folding the newly synthesized and deformed proteins; prevention and reversal of aggregation; translocation of proteins across organelles membranes; assembly and disassembly of oligomeric structures and control of the biological activity of regulators proteins. In humans, the high activity of Hsp70 is involved in several pathologies, however, little is known about the role of these Hsp in intracellular parasites. The aim of this project is the understanding of the mechanism of cytoplasmic and mitochondrial Hsp70 (mtHsp70) and co-chaperones of two important human parasites: Plasmodium falciparum and Leishmania braziliensis, etiologic agents of malaria and leishmaniasis, respectively. In this context, the interaction of Hsp70 and mtHsp70 with co-chaperones as well as ligands/inhibitors will be also analyzed. The human system, well known, will be used for comparative studies. For this purpose, molecular biology, biochemical and biophysical techniques will be applied in order to elucidate the role of (mt)Hsp70 machinery in those parasites to contribute with relevant information towards a future control of these important parasitic diseases.